Ameliorative effect of betanin on experimental cisplatin-induced liver injury; the novel impact of miRNA-34a on the SIRT1/PGC-1α signaling pathway.

Autor: El Shaffei I; Biochemistry Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Abdel-Latif GA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Farag DB; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt., Schaalan M; Pharmacy Practice and Clinical Pharmacy Department, Translational and Clinical Research Unit, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt., Salama RM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Jun; Vol. 35 (6), pp. 1-14. Date of Electronic Publication: 2021 Mar 04.
DOI: 10.1002/jbt.22753
Abstrakt: The anticancer agent, cisplatin (CIS), is associated with hepatotoxic effects related to activation of oxidative stress and inflammation pathways. CIS-induced oxidative DNA damage reduces sirtuin 1 (SIRT1) activity, which in turn, modulates the activity of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). Moreover, microRNA-34a (miRNA-34a) was shown to hinder both SIRT1 and nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Thus, targeting such a pathway can alleviate CIS-induced hepatotoxicity. Betanin (BET) is a natural red glycoside food dye obtained from beets, which is reported to exhibit antioxidant function. However, its role in CIS-induced liver injury and the molecular mechanism has not been fully elucidated. Thus, the aim of this study was to investigate the ameliorative effect of BET on CIS-induced acute hepatotoxicity through the SIRT1/PGC-1α signaling pathway and illustrate the impact of miRNA-34a. Seventy-two rats were divided into six equal groups: (1) Control, (2) BET, (3) CIS, (4) CIS/BET, (5) CIS/EX527, and (6) CIS/BET/EX527. CIS-induced liver injury was evidenced by deregulated BAX and BCL2 levels, decreased levels of AMP-activated protein kinase and PGC-1α expression, and decreased SIRT1 activity. Consequently, reduced levels of Nrf2 and the expression of associated heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were observed. Intriguingly, BET succeeded in reducing the CIS-induced liver injury through reducing miRNA-34a expression and enhancing the SIRT1/PGC-1α pathway. These findings coincide with the molecular docking results and the histopathological picture. In conclusion, the current research provided novel findings of the BET ameliorative effect on CIS-induced liver injury through modulating miRNA-34a expression and the SIRT1/PGC-1α signaling cascade.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: